In humans, traumatic social experiences can contribute to psychiatric disorders¹. It is suggested that social trauma impairs brain reward function such that social behaviour is no longer rewarding, leading to severe social avoidance^2,3. In rodents, the chronic social defeat stress (CSDS) model has been used to understand the neurobiology underlying stress susceptibility versus resilience following social trauma, yet little is known regarding its impact on social reward^4,5. Here we show that, following CSDS, a subset of male and female mice, termed susceptible (SUS), avoid social interaction with non-aggressive, same-sex juvenile C57BL/6J mice and do not develop context-dependent social reward following encounters with them. Non-social stressors have no effect on social reward in either sex. Next, using whole-brain Fos mapping, in vivo Ca²⁺ imaging and whole-cell recordings, we identified a population of stress/threat-responsive lateral septum neurotensin (NT^LS) neurons that are activated by juvenile social interactions only in SUS mice, but not in resilient or unstressed control mice. Optogenetic or chemogenetic manipulation of NT^LS neurons and their downstream connections modulates social interaction and social reward. Together, these data suggest that previously rewarding social targets are possibly perceived as social threats in SUS mice, resulting from hyperactive NT^LS neurons that occlude social reward processing.

在人类中，创伤性社会经历会导致精神疾病¹。有人建议，社会创伤会损害大脑奖赏功能，使社会行为不再有益，从而导致严重的社会回避^2,3。在啮齿类动物中，慢性社会失败压力 (CSDS) 模型已被用于了解社会创伤后压力敏感性与恢复力之间的神经生物学，但对其对社会奖励的影响知之甚少^4,5. 在这里，我们表明，在 CSDS 之后，雄性和雌性小鼠的一个子集，称为易感 (SUS)，避免与非攻击性的同性幼年 C57BL/6J 小鼠进行社交互动，并且在遇到他们。非社会压力源对两性的社会奖励都没有影响。接下来，使用全脑 Fos 映射、体内 Ca ²⁺成像和全细胞记录，我们确定了一群压力/威胁反应侧隔神经降压素 (NT ^LS ) 神经元，这些神经元仅在 SUS 小鼠中被幼年社交互动激活, 但不是在有弹性或无压力的控制小鼠中。NT ^{LS的光遗传学或化学遗传学操作}神经元及其下游连接调节社会互动和社会奖励。总之，这些数据表明，先前奖励性社会目标可能被 SUS 小鼠视为社会威胁，这是由于过度活跃的 NT ^LS神经元阻碍了社会奖励处理。